Tracking cortical excitability dynamics with transcranial magnetic stimulation in focal epilepsy

Annals of Clinical and Translational Neurology, vol. 9, pp. 540–551

Abstract

INTRODUCTION: The lack of reliable biomarkers constrain epilepsy management. We assessed the potential of repeated transcranial magnetic stimulation with electromyography (TMS-EMG) to track dynamical changes in cortical excitability on a within-subject basis. METHODS: We recruited people with refractory focal epilepsy who underwent video-EEG monitoring and drug tapering as part of the presurgical evaluation. We performed daily TMS-EMG measurements with additional postictal assessments 1-6 h following seizures to assess resting motor threshold (rMT), and motor evoked potentials (MEPs) with single- and paired-pulse protocols. Anti-seizure medication (ASM) regimens were recorded for the day before each measurement and expressed in proportion to the dosage before tapering. Additional measurements were performed in healthy controls to evaluate day-to-day rMT variability. RESULTS: We performed 77 (58 baseline, 19 postictal) measurements in 16 people with focal epilepsy and 35 in seven healthy controls. Controls showed minimal day-to-day rMT variation. Withdrawal of ASMs was associated with a lower rMT without affecting MEPs of single- and paired-pulse TMS-EMG paradigms. Postictal measurements following focal to bilateral tonic-clonic seizures demonstrated unaltered rMT and increased short interval intracortical inhibition, while measurements following focal seizures with impaired awareness showed decreased rMT's and reduced short and long interval intracortical inhibition. CONCLUSION: Serial within-subject rMT measurements yielded reproducible, stable results in healthy controls. ASM tapering and seizures had distinct effects on TMS-EMG excitability indices in people with epilepsy. Drug tapering decreased rMT, indicating increased overall corticospinal excitability, whereas seizures affected intracortical inhibition with contrasting effects between seizure types.

Authors 6

1. Robert M. Helling

   Stichting Epilepsie Instellingen Nederland

   Affiliation as printed

   Stichting Epilepsie Instellingen Nederland (SEIN) Heemstede The Netherlands

   Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands

2. Sharon Shmuely

   UCL Biomedical Research Centre · National Hospital for Neurology and Neurosurgery · Stichting Epilepsie Instellingen Nederland · UCL Queen Square Institute of Neurology · University College London

   Affiliation as printed

   NIHR University College London Hospitals Biomedical Research Centre UCL Institute of Neurology Queen Square London UK

   Stichting Epilepsie Instellingen Nederland (SEIN) Heemstede The Netherlands

   NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, Queen Square, London, UK

   Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands

3. Prisca Rachel Bauer

   University of Freiburg · University Medical Center Freiburg

   Affiliation as printed

   Department of Psychosomatic Medicine and Psychotherapy University Medical Center Freiburg Germany

   Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Freiburg, Germany

4. Else A. Tolner Aachen Department of Human Genetics Leiden University Medical Centre Leiden The Netherlands Department of Neurology Leiden University Medical Centre Leiden The Netherlands Department of Human Genetics Department of Neurology, Leiden University Medical Centre

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics Leiden University Medical Centre Leiden The Netherlands

   Department of Neurology Leiden University Medical Centre Leiden The Netherlands

   Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands

   Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands

5. Gerhard H. Visser

   Stichting Epilepsie Instellingen Nederland

   Affiliation as printed

   Stichting Epilepsie Instellingen Nederland (SEIN) Heemstede The Netherlands

   Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands

6. Roland D. Thijs corresponding Aachen Department of Neurology Leiden University Medical Centre Leiden The Netherlands Department of Neurology, Leiden University Medical Centre

   Leiden University · Leiden University Medical Center · UCL Biomedical Research Centre · National Hospital for Neurology and Neurosurgery · Stichting Epilepsie Instellingen Nederland · UCL Queen Square Institute of Neurology · University College London

   Affiliation as printed

   Department of Neurology Leiden University Medical Centre Leiden The Netherlands

   NIHR University College London Hospitals Biomedical Research Centre UCL Institute of Neurology Queen Square London UK

   Stichting Epilepsie Instellingen Nederland (SEIN) Heemstede The Netherlands

   Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands

   NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, Queen Square, London, UK

   Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands